An estimated one third of the world's population is infected with Mycobacterium tuberculosis, and it is the leading cause of death among adults by an infectious disease worldwide. TB control using DOTS (Directly Observed Short Therapy, short course) to successfully diagnose, treat and follow sputum-smear positive TB cases is a priority of the World Health Organization (WHO), but there is growing recognition that DOTS alone will not be enough to control or eradicate TB given the extended duration of treatment and the emergence of drug-resistant forms of M. tuberculosis. New methods are needed to quantify the impact of ongoing TB transmission and the importance of preventive strategies. The focus of this research will be an evaluation of community- based TB transmission dynamics at a field site in Southern Mexico. Molecular epidemiology provides important insights into the transmission dynamics of tuberculosis, but because it relies upon mycobacterial cultures, it can only track active cases. The proposed research will integrate conventional tuberculin skin test survey methodology into an ongoing population-based research project so that we may track infection as well as disease and test hypotheses about alternative strategies for controlling TB infection.
The specific aims are: 1) to describe the epidemiology of TB infection caused by culture-confirmed cases of M. tuberculosis; 2) to identify risk factors for TB infection, stratified by the biologic characteristics of the strains of M. tuberculosis and the gender, age group, and social setting of the index cases; 3) to determine the specificity and predictive value of contact tracing by comparing the RFLP patterns of cases and those arising among their contacts; and 4) to develop cost- effectiveness models of appropriate screening strategies and interventions to control TB infection. The research will also generate important baseline data for the future testing of new diagnostics and vaccines. This project will provide an ideal vehicle for additional, mentored training and research to develop the PI's long standing career interest in international infectious disease research. The grant award will build on previous work and provide training in areas new to the candidate, such as biomedical techniques and cost-effectiveness modeling. Her technical training in epidemiology and biostatistics, prior epidemiologic research studies, and extensive familiarity with Latin America fit perfectly with the strengths and needs of a well established field site in Veracruz, Southern Mexico.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01TW000001-03
Application #
6394891
Study Section
International and Cooperative Projects 1 Study Section (ICP)
Program Officer
Jessup, Christine
Project Start
1999-09-30
Project End
2003-08-31
Budget Start
2001-09-01
Budget End
2003-08-31
Support Year
3
Fiscal Year
2001
Total Cost
$75,600
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Torres, Martha; García-García, Lourdes; Cruz-Hervert, Pablo et al. (2015) Effect of isoniazid on antigen-specific interferon-? secretion in latent tuberculosis. Eur Respir J 45:473-82
Bastos, Mayara L; Hussain, Hamidah; Weyer, Karin et al. (2014) Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first- and second-line drugs: an individual patient data meta-analysis. Clin Infect Dis 59:1364-74
Bonacci, Robert A; Cruz-Hervert, Luis Pablo; García-García, Lourdes et al. (2013) Impact of cigarette smoking on rates and clinical prognosis of pulmonary tuberculosis in Southern Mexico. J Infect 66:303-12
Migliori, G B; Sotgiu, G; Gandhi, N R et al. (2013) Drug resistance beyond extensively drug-resistant tuberculosis: individual patient data meta-analysis. Eur Respir J 42:169-179
Falzon, Dennis; Gandhi, Neel; Migliori, Giovanni B et al. (2013) Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes. Eur Respir J 42:156-68
Sullivan, Timothy; Ben Amor, Yanis (2013) What's in a name? The future of drug-resistant tuberculosis classification. Lancet Infect Dis 13:373-6
Jiménez-Corona, María Eugenia; Cruz-Hervert, Luis Pablo; García-García, Lourdes et al. (2013) Association of diabetes and tuberculosis: impact on treatment and post-treatment outcomes. Thorax 68:214-20
Ahuja, Shama D; Ashkin, David; Avendano, Monika et al. (2012) Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients. PLoS Med 9:e1001300
Cruz-Hervert, Luis Pablo; Garcia-Garcia, Lourdes; Ferreyra-Reyes, Leticia et al. (2012) Tuberculosis in ageing: high rates, complex diagnosis and poor clinical outcomes. Age Ageing 41:488-95
Marquina-Castillo, Brenda; García-García, Lourdes; Ponce-de-León, Alfredo et al. (2009) Virulence, immunopathology and transmissibility of selected strains of Mycobacterium tuberculosis in a murine model. Immunology 128:123-33

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